Candidate Serum Biomarkers of Neural Injury and Neuroinflammation in Childhood Epilepsy: Comparison Between Controlled and Drug-Resistant Phenotypes

Background: This study aimed to compare serum levels of nitric oxide (NO) related metabolites, glial fibrillary acidic protein (GFAP), and ubiquitin (UBI) between children with controlled epilepsy (CE) and drug-resistant epilepsy (DRE) of unknown etiology, and to investigate the associations between these biomarkers and electroclinical features. Methods: Eighty-five children aged 2–18 years with epilepsy of unknown etiology who had been receiving antiseizure treatment for at least six months were enrolled; 58 were classified as CE and 27 as DRE. Serum GFAP and UBI concentrations were measured using enzyme-linked immunosorbent assay, and serum NO-related metabolites were assessed using a Griess-based colorimetric assay. Between-group comparisons were performed using the Mann–Whitney U test, and associations between biomarkers and clinical variables were evaluated using Spearman rank correlation analysis. Bonferroni correction was applied for multiple comparisons. Results: Historical seizure frequency, comorbidity rate, and seizure detection on initial video-EEG differed significantly between the CE and DRE groups. However, serum NO-related metabolite, GFAP, and UBI levels did not differ significantly between the CE and DRE groups. Correlation analyses revealed a significant positive correlation between serum NO-related metabolite levels and age exclusively in the DRE group (ρ = 0.594, p = 0.001), which remained significant after Bonferroni correction. No such association was observed in the CE group. Conclusion: No statistically significant differences in the measured peripheral serum biomarkers were detected between the CE and DRE groups in this sample. The age-related increase in NO-related metabolites observed in the DRE group should be interpreted cautiously and does not establish progressive NO upregulation or cumulative neuroinflammatory burden. Studies incorporating a healthy control group, standardized sampling intervals, and longitudinal designs are needed to clarify the clinical utility of these biomarkers in childhood epilepsy.